Li Cheng-Wei, Chu Yung-Hsiang, Chen Bor-Sen
Lab. of Systems biology, National Tsing Hua University, Hsinchu, 300, Taiwan.
Cancer Inform. 2007 Feb 18;2:223-41.
Cell cycle is an important clue to unravel the mechanism of cancer cells. Recently, expression profiles of cDNA microarray data of Cancer cell cycle are available for the information of dynamic interactions among Cancer cell cycle related genes. Therefore, it is more appealing to construct a dynamic model for gene regulatory network of Cancer cell cycle to gain more insight into the infrastructure of gene regulatory mechanism of cancer cell via microarray data.
Based on the gene regulatory dynamic model and microarray data, we construct the whole dynamic gene regulatory network of Cancer cell cycle. In this study, we trace back upstream regulatory genes of a target gene to infer the regulatory pathways of the gene network by maximum likelihood estimation method. Finally, based on the dynamic regulatory network, we analyze the regulatory abilities and sensitivities of regulatory genes to clarify their roles in the mechanism of Cancer cell cycle.
Our study presents a systematically iterative approach to discern and characterize the transcriptional regulatory network in Hela cell cycle from the raw expression profiles. The transcription regulatory network in Hela cell cycle can also be confirmed by some experimental reviews. Based on our study and some literature reviews, we can predict and clarify the E2F target genes in G1/S phase, which are crucial for regulating cell cycle progression and tumorigenesis. From the results of the network construction and literature confirmation, we infer that MCM4, MCM5, CDC6, CDC25A, UNG and E2F2 are E2F target genes in Hela cell cycle.
细胞周期是揭示癌细胞机制的重要线索。最近,癌细胞周期的cDNA微阵列数据的表达谱可用于了解癌细胞周期相关基因之间的动态相互作用信息。因此,构建癌细胞周期基因调控网络的动态模型以通过微阵列数据更深入地了解癌细胞基因调控机制的基础结构,更具吸引力。
基于基因调控动态模型和微阵列数据,我们构建了癌细胞周期的完整动态基因调控网络。在本研究中,我们通过最大似然估计方法追溯目标基因的上游调控基因,以推断基因网络的调控途径。最后,基于动态调控网络,我们分析调控基因的调控能力和敏感性,以阐明它们在癌细胞周期机制中的作用。
我们的研究提出了一种系统的迭代方法,从原始表达谱中识别和表征Hela细胞周期中的转录调控网络。Hela细胞周期中的转录调控网络也可以通过一些实验综述得到证实。基于我们的研究和一些文献综述,我们可以预测和阐明G1/S期的E2F靶基因,这些基因对于调节细胞周期进程和肿瘤发生至关重要。从网络构建和文献证实的结果来看,我们推断MCM4、MCM5、CDC6、CDC25A、UNG和E2F2是Hela细胞周期中的E2F靶基因。